Hypothyroidism

Hypothyroidism (low T3, T4 ,,, high TSH) • Hypothyroidism: is decreased level of T4 (tetraiodothyronine/thyroxine), T3 (triiodothyronine) and elevated TSH. • High TSH because of the positive feedback of the low T3, T4. • TSH is probably the best screening test for thyroid disease. • It’s very serious that’s why nowadays any newborn should have (T3, T4, TSH) test, so that hypothyroidism can be detected early on to avoid development of Cretinism, hypothyroidism in children, young patients. • Thyroid gland is necessary in adults and children, growing up children need thyroid hormones for normal development and normal CNS function. • Untreated hypothyroidism will end up being severe and patients may be mentally retarded. ❖ Cretinism: patient is obese, big tongue outside. We should not see it nowadays because all newborns are screened for it. ❖ Myxedema: hypothyroidism in adults at the age of 15-20. ▪ Cold intolerance: temperature is high, but patient still feels cold. ▪ Overweight: patient doesn’t eat too much but gains weight because of the low metabolic rate, no energy expenditure. ▪ Cool pale thick skin especially in chin. ▪ Opposite of hyperthyroidism. (For example; here we have constipation while in hyperthyroidism it is diarrhea). Page | 2 Page | 3 Causes of hypothyroidism: The disease in the thyroid itself End organ resistance Normal thyroid Notes about the table above: o Ablation (most common cause): damage either by surgery, radioiodine therapy or external irradiation in the neck, for example: carcinoma of the larynx. o If Hashimoto thyroiditis is not treated it ends up with fibrosis and hypothyroidism. o Areas away from the sea may have iodine deficiency, rare to see nowadays because we have iodinated salts. o Lithium: A drug used for bipolar disorders to stabilize mood. o In the case of pituitary adenoma: remove pituitary gland → no TSH → secondary hypothyroidism → long life thyroxine replacement therapy. o Hypothalamic failure: TRH is not secreted → TSH is not secreted → T3 and T4 are not secreted. Page | 4 *Extremely important to differentiate between both of them. ➢ Severe untreated hypothyroidism is one of the causes of depression. ➢ 3pm crash: afternoon those patients feel extremely tired. ➢ When you see these symptoms, you start to investigate to diagnose the patient with hypothyroidism or hyperthyroidism. Page | 5 Autoimmune thyroid diseases ** important Hashimoto thyroditis (prototype) Granulomatous thyroditis (De Quervain) Subacute lumphocytic thyroiditis Hashimoto Thyroiditis (Chronic Lymphocytic Thyroiditis) ➢ It’s a common chronic disease. ➢ Most common cause of hypothyroidism in areas with no iodine deficiency. (Considering that there is no iodine deficiency in the world, it’s the most common cause of hypothyroidism). ➢ Gradual hypothyroidism (rarely initial transient Hashitoxicosis). It doesn’t happen suddenly, starts with the inflammatory response → increased T3, T4 → euthyroid → hypothyroid → chronicity (repair and fibrosis) thyroid become fibrotic no secretion of T3, T4 → hypothyroidism. (Hashitoxicosis → initial thyrotoxicosis due to Hashimoto) ➢ More common in middle aged females (45-60 years). ➢ Autoimmune destruction of thyroid epithelial cells, anti-thyroid antibodies (serological test: anti-thyroid antibodies) ➢ 4-6 times increased risk for papillary thyroid carcinoma (most common malignancy in thyroid) and B-cell NH lymphoma (primary non-Hodgkin). Page | 6 Pathogenesis: ❖ Some factors that induce autoimmunity causes your immune system to get stimulated to damage your own thyroid cells. ❖ Anti-thyroid antibodies are not the only mechanism leading to Hashimoto thyroiditis there is also T cell mediated cytotoxicity ( CD8+ T cells) and thyrocyte injury (CD4+ TH1 cells) but there is no test for these two. ❖ That’s why sometimes the anti-thyroid antibodies test is negative, but the patient has Hashimoto thyroiditis because of one of the other mechanisms. ****not all Hashimoto thyroiditis patients are anti-thyroid antibodies positive. **** T/F: 100% of patients have circulating antibodies  FALSE Page | 7 Histologically: Severe chronic lymphocytic thyroiditis Hurthle cells change Lymph node follicle with germinal center Colloid Thyroid Follicles between them C-cells (parafollicular cells) that produce calcitonin. ❖ Thyroid endocrine organ secretes 2 major hormones: 1) T3, T4 together from follicular and epithelial cells. 2) Calcitonin from parafollicular cells. ❖ 2 different cancers can happen in the thyroid gland: 1) Thyroid cancer → cell of origin: follicular cells. 2) Medullary thyroid carcinoma (MTC) → cell of origin: para-follicular cells. ❖ Colloid: pink material (eosinophilic) where there are no cells only proteins and raw materials (iodine one of them) used to synthesize hormones (T3, T4). ❖ Hurthle cell change (oncocytic cell change) in the epithelial cells of thyroid cytoplasm become larger and granular and full of mitochondria; that’s why it’s pink (eosinophilic) can be seen in histology and fine needle aspiration (FNA). Page | 8 Histological features of Hashimoto thyroiditis: 1- Lymphocytic thyroiditis 2- Hurthle cell change. Diagnosis: clinical presentation → serological test → histology. Subacute Granulomatous (de quervain) Thyroiditis ➢ Granulomatous thyroiditis, more acute with neck pain, firm thyroid. (Differs from Hashimoto that it’s painful), Patient came with painful anterior neck swelling and fine needle aspiration revealed colloid and granulomas → subacute granulomatous. ➢ Chronic specific type of inflammation, not acute. ➢ Could be virally associated or induced but the etiology is unknown. ➢ More common in middle aged females, 30-50 years. ➢ Maybe initial transient thyrotoxicosis (doesn’t last long) followed by hypothyroidism ➢ Self-limiting disease (6-8 weeks), either self-limited or there will be thyroid damage and there will be hypothyroidism → replacement therapy and watch for future malignancy. OTHER LESS COMMON THYROIDITIS: Subacute lymphocytic thyroiditis: ➢ ➢ ➢ ➢ ➢ ➢ ➢ Some believes that it’s a variant of Hashimoto. Middle aged women. Post-partum. Initial transient thyrotoxicosis then gradual hypothyroidism. Autoimmune with circulating antibodies. Gland is usually normal size (no mass). Lymphocytic thyroiditis no hurthle cells; that’s why Hashimoto is excluded. Page | 9 Riedel thyroiditis: ➢ IgG4 associated disease can occur anywhere (pancreas, mesentery,…) there would be a lot of plasma cells full of IgG4 which cause sclerosis (fibrosis). ➢ What’s special about it is: stony-hard thyroid due to severe fibrosis, so thyroid is destructed >> Hypothyroidism >> decreased T3, T4, increased TSH and no antibodies (even CD4, CD8 are negative). ➢ Very rare and not easy to diagnose. Graves Disease (diffuse toxic goiter) ➢ Described by Robert Graves in 1835. ➢ Most common cause of endogenous hyperthyroidism. ➢ Triad for the diagnosis: thyrotoxicosis (high T3, T4, low TSH) + ophthalmopathy (exophthalmos) + dermopathy (pretibial myxedema) specially in the chin. ➢ Autoimmune, HLA-DR3 and CTLA-4. ➢ High homogenous radioactive iodine uptake. ➢ Women, 20-40 years. Page | 10 Autoantibodies for Graves disease: ❖ Autoantibodies bind to TSH receptor and inhibit the negative feedback → continuous secretion of T3, T4. +Sometimes TSH-binding inhibitor Ig, may cause hypothyroidism (written in the slides but doctor said forget about it) Scalloping follicles (colloid is white) indicates hyperactivity, a characteristic of thyroid disease Follicular epithelial cells take the colloid to synthesize T3, T4. Papillary hyperplasia Page | 11 ❖ Complications should not be seen nowadays; because of early detection. Exophthalmos Pretibial myxedema Diffuse and Multinodular Goiter: ➢ Very common; most common thyroid disease (euthyroid MNG). ➢ Thought to be caused because of impaired hormone synthesis, iodine deficiency, but the etiology is unknown. ➢ Sometimes high TSH, hyperplasia & hypertrophy. ➢ In most cases; euthyroid no problem in T3, T4 or TSH; rarely goitrous hypothyroidism. ➢ Endemic or sporadic. ➢ More common in Females ➢ Initially diffuse then multinodular. ➢ Clinically: mass effects, pressure symptoms (difficulty in swallowing, drinking, and snoring at night) and cosmetic. ➢ Rare: toxic MNG (Plummer syndrome). Page | 12 euthyroid Nodules and hemorrhage Page | 13